Efficient inhibition of human telomerase activity by antisense oligonucleotides sensitizes cancer cells to radiotherapy
Efficient inhibition of human telomerase activity by antisense oligonucleotides sensitizes cancer cells to radiotherapy
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DOI：
10.1111/j.1745-7254.2006.00417.x
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发表时间：
2006-09-01
影响因子：
8.2
通讯作者：
Zhou, Yun-feng
中科院分区：
文献类型：
--
作者：
Ji, Xue-mei;Xie, Cong-hua;Zhou, Yun-feng
目的：研究人端粒酶RNA （hTR）特异性反义寡核苷酸（ASODN）对非人神经胶质瘤细胞（U251）的放射增敏和增殖抑制作用。方法：用hTR ASODN或非特异性寡核苷酸（NSODN）转染U251细胞。采用端粒重复扩增法（TRAP-PCR-ELISA）检测co -60 γ射线辐照前后端粒酶活性，采用彗星法检测DNA损伤和修复情况。采用经典菌落法绘制细胞存活曲线，检测Do值。结果：hTR反义寡核苷酸可下调端粒酶活性，增加辐射诱导的DNA损伤，减少后续修复。此外，它还能抑制细胞增殖，降低Do值，显示出更高的放射敏感性。然而，端粒长度在短时间内没有变化。结论：本研究提示基于asodn的端粒酶抑制剂可用于开发有效的增敏放疗。
Aim: To investigate the effect of the antisense oligonucleotides (ASODN) specific for human telomerase RNA (hTR) on radio sensitization and proliferation inhibition inhuman neurogliocytoma cells (U251). Methods: U251 cells were transfected with hTR ASODN or nonspecific oligonucleotides.(NSODN). Before and after irradiation of Co-60-gamma ray, telomerase activity was assayed by telomeric repeat amplification protocol (TRAP-PCR-ELISA), and DNA damage and repair were examined by the comet assay. The classical colony assay was used to plot the cell-survival curve, to detect the Do value. Results: hTR antisense oligonucleotides could downregulate the telomerase activity, increase radiation induced DNA damage and reduce the subsequent repair. Furthermore, it could inhibit the proliferation and decrease the Do value which demonstrates rising radiosensitivity. However, telomere length was unchanged over a short period of time. Conclusion: These findings suggest that an ASODN-based strategy may be used to develop telomerase inhibitors, which can efficiently sensitize radiotherapy.